My group recently identified Vcsa1 as a potential biomarker for vascular complications of diabetes leading to erectile dysfunction (ED). We demonstrated that Vcsa1 is one of the most downregulated genes in the corpora of diabetic rats. We have also shown that a potential human homologue of this gene (hSMR3A) is downregulated in diabetic patient orporal samples. Our published studies demonstrate that the mature peptide product of Vcsa1 (sialorphin) plays a role in regulating corporal smooth muscle tone and potentially the same mechanisms may also function in regulating other vascular tissues tone. We hypothesize that level of expression of Vcsa1 (and its human homologue, hSMR3A) and their protein products, can act as markers for the vascular complications of diabetes. Our experiments are designed to confirm this hypothesis in animal models and from atient samples. In animal experiments we will determine how diabetes effects the expression of Vcsa1 using quantitative RT-PCR in vascular tissues and correlate the expression of Vcsa1 to the severity of diabetes We will also determine if diabetes effects the expression of sialorphin in the bloodstream and saliva of diabetic animals using immunoassays.
Our second aim will be to develop an antibody against the protein product of hSMR3A (the human homologue of Vcsa1). Using this antibody we will investigate the expression and processing of the hSMR3A product using MALDI-TOFF spectroscopy. This will allow us to develop an effective immunoassay for use in patients.
The final aim will be to determine expression levels of hSMR3A protein from diabetic and non-diabetic patients (in saliva, blood and corporal samples) as an indicator of vascular health. ? ? ?
